PaCO2 Association with Outcomes of Patients with Traumatic Brain Injury at High Altitude: A Prospective Single-Center Cohort Study.

BACKGROUND: Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. METHODS: This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. RESULTS: We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. CONCLUSIONS: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

Epidural stimulation restores muscle synergies by modulating neural drives in participants with sensorimotor complete spinal cord injuries.

Multiple studies have corroborated the restoration of volitional motor control after motor-complete spinal cord injury (SCI) through the use of epidural spinal cord stimulation (eSCS), but rigorous quantitative descriptions of muscle coordination have been lacking. Six participants with chronic, motor and sensory complete SCI underwent a brain motor control assessment (BMCA) consisting of a set of structured motor tasks with and without eSCS. We investigated how muscle activity complexity and muscle synergies changed with and without stimulation. We performed this analysis to better characterize the impact of stimulation on neuromuscular control. We also recorded data from nine healthy participants as controls. Competition exists between the task origin and neural origin hypotheses underlying muscle synergies. The ability to restore motor control with eSCS in participants with motor and sensory complete SCI allows us to test whether changes in muscle synergies reflect a neural basis in the same task. Muscle activity complexity was computed with Higuchi Fractal Dimensional (HFD) analysis, and muscle synergies were estimated using non-negative matrix factorization (NNMF) in six participants with American Spinal Injury Association (ASIA) Impairment Score (AIS) A. We found that the complexity of muscle activity was immediately reduced by eSCS in the SCI participants. We also found that over the follow-up sessions, the muscle synergy structure of the SCI participants became more defined, and the number of synergies decreased over time, indicating improved coordination between muscle groups. Lastly, we found that the muscle synergies were restored with eSCS, supporting the neural hypothesis of muscle synergies. We conclude that eSCS restores muscle movements and muscle synergies that are distinct from those of healthy, able-bodied controls.

Mapping Spinal Cord Stimulation-Evoked Muscle Responses in Patients With Chronic Spinal Cord Injury.

OBJECTIVES: Epidural spinal cord stimulation (eSCS) has shown promise for restoring some volitional motor control after spinal cord injury (SCI). Maximizing therapeutic response requires effective spatial stimulation generated through careful configuration of anodes and cathodes on the eSCS lead. By exploring the way the spatial distribution of low frequency stimulation affects muscle activation patterns, we investigated the spatial specificity of stimulation-evoked responses for targeted muscle groups for restoration after chronic SCI (cSCI) in participants in the Epidural Stimulation After Neurologic Damage (E-STAND) trial. MATERIALS AND METHODS: Fifteen participants with Abbreviated Injury Scale A cSCI from the E-STAND study were evaluated with a wide range of bipolar spatial patterns. Surface electromyography captured stimulation-evoked responses from the rectus abdominis (RA), intercostal, paraspinal, iliopsoas, rectus femoris (RF), tibialis anterior (TA), extensor hallucis longus (EHL), and gastrocnemius muscle groups bilaterally. Peak-to-peak amplitudes were analyzed for each pulse across muscles. Stimulation patterns with dipoles parallel (vertical configurations), perpendicular (horizontal configurations), and oblique (diagonal configurations) relative to the rostral-caudal axis were evaluated. RESULTS: Cathodic stimulation in the transverse plane indicated ipsilaterally biased activation in RA, intercostal, paraspinal, iliopsoas, RF, TA, EHL, and gastrocnemius muscles (p < 0.05). We found that caudal cathodic stimulation was significantly more activating only in the RF and EHL muscle groups than in the rostral (p < 0.037 and p < 0.006, respectively). Oblique stimulation was found to be more activating in the RA, intercostal, paraspinal, iliopsoas, and TA muscle groups than in the transverse (p < 0.05). CONCLUSIONS: Cathodic stimulation provides uniform specificity for targeting laterality. Few muscle groups responded specifically to variation in rostral/caudal stimulation, and oblique stimulation improved stimulation responses when compared with horizontal configurations. These relations may enable tailored targeting of muscle groups, but the surprising amount of variation observed suggests that monitoring these evoked muscle responses will play a key role in this tailoring process. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03026816.

The safety of epidural spinal cord stimulation to restore function after spinal cord injury: post-surgical complications and incidence of cardiovascular events.

STUDY DESIGN: Cohort prospective study. OBJECTIVES: Epidural spinal cord stimulation (eSCS) improves volitional motor and autonomic function after spinal cord injury (SCI). While eSCS has an established history of safety for chronic pain, it remains unclear if eSCS in the SCI population presents the same risk profile. We aimed to assess safety and autonomic monitoring data for the first 14 participants in the E-STAND trial. SETTING: Hennepin County Medical Center, Minneapolis and Minneapolis Veterans Affairs Medical Center, Minnesota, USA. METHODS: Monthly follow-up visits assessed surgical and medical device-related safety outcomes as well as stimulation usage. Beat-by-beat blood pressure (BP) and continuous electrocardiogram data were collected during head-up tilt-table testing with and without eSCS. RESULTS: All participants had a motor-complete SCI. Mean (SD) age and time since injury were 38 (10) and 7 (5) years, respectively. There were no surgical complications but one device malfunction 4 months post implantation. Stimulation was applied for up to 23 h/day, across a broad range of parameters: frequency (18-700 Hz), pulse width (100-600 µs), and amplitude (0.4-17 mA), with no adverse events reported. Tilt-table testing with eSCS demonstrated no significant increases in the incidence of elevated systolic BP or a greater frequency of arrhythmias. CONCLUSIONS: eSCS to restore autonomic and volitional motor function following SCI has a similar safety profile as when used to treat chronic pain, despite the prevalence of significant comorbidities and the wide variety of stimulation parameters tested.

Litigation risks despite guideline adherence for acute spinal cord injury: time is spine.

OBJECTIVE: Current guidelines do not specify timing for management of acute spinal cord injury (aSCI) due to lack of high-quality evidence supporting specific intervals for intervention. Randomized prospective trials may be unethical. Nonetheless, physicians have been sued for delays in diagnosis and intervention. METHODS: The authors reviewed both the medical literature supporting the guidelines and the legal cases reported in the Westlaw and Lexis Advance databases from 1972 to 2018 resulting in awards or settlements, to identify whether surgeons are vulnerable to litigation despite the existence of guidelines not mandating specific timing of care. RESULTS: Timing of intervention was related to claims in 59 (36%) of 163 cases involving SCI. All 22 trauma cases identified cited timing of intervention, sometimes related to delayed diagnosis, as a reason for the lawsuit. The mean award of 10 cases in which the plaintiffs' awards were disclosed was $4,294,384. In the majority of cases, award amounts were not disclosed. CONCLUSIONS: Because conduct of a prospective, randomized trial to investigate surgical timing of intervention for aSCI may not be achievable, evidence-based guidelines will be unlikely to mandate specific timing. Nonetheless, surgeons who unreasonably delay intervention for aSCI may be at risk for litigation due to treatment delay. This is increasingly likely in an environment where "complete" SCI is difficult to verify. SCI may at some point be recognized as a surgical emergency, as brain injury generally is, despite a lack of prospective randomized trials supporting this implementation, challenging the feasibility of the US trauma infrastructure to provide care for these patients.

Eye Tracking as a Biomarker for Concussion in Children.

OBJECTIVE: Concussion is the most common type of brain injury in both pediatric and adult populations and can potentially result in persistent postconcussion symptoms. Objective assessment of physiologic "mild" traumatic brain injury in concussion patients remains challenging. This study evaluates an automated eye-tracking algorithm as a biomarker for concussion as defined by its symptoms and the clinical signs of convergence insufficiency and accommodation dysfunction in a pediatric population. DESIGN: Cross-sectional case-control study. SETTING: Primary care. PATIENTS: Concussed children (N = 56; mean age = 13 years), evaluated at a mean of 22-week post-injury, compared with 83 uninjured controls. INDEPENDENT VARIABLES: Metrics comparing velocity and conjugacy of eye movements over time were obtained and were compared with the correlation between Acute Concussion Evaluation (ACE) scores, convergence, and accommodation dysfunction. MAIN OUTCOME MEASURES: Subjects' eye movements recorded with an automated eye tracker while they watched a 220-second cartoon film clip played continuously while moving within an aperture. RESULTS: Twelve eye-tracking metrics were significantly different between concussed and nonconcussed children. A model to classify concussion as diagnosed by its symptoms assessed using the ACE achieved an area under the curve (AUC) = 0.854 (71.9% sensitivity, 84.4% specificity, a cross-validated AUC = 0.789). An eye-tracking model built to identify near point of convergence (NPC) disability achieved 95.8% specificity and 57.1% sensitivity for an AUC = 0.810. Reduced binocular amplitude of accommodation had a Spearman correlation of 0.752(P value <0.001) with NPC. CONCLUSION: Eye tracking correlated with concussion symptoms and detected convergence and accommodative abnormalities associated with concussion in the pediatric population. It demonstrates utility as a rapid, objective, noninvasive aid in the diagnosis of concussion.

23.4% Hypertonic Saline and Intracranial Pressure in Severe Traumatic Brain Injury Among Children: A 10-Year Retrospective Analysis.

OBJECTIVE: To explore the effect of 23.4% hypertonic saline for management of elevated intracranial pressure in children admitted to our institution for severe traumatic brain injury. DESIGN: Single-center, retrospective medical chart analysis. SETTING: A PICU at a level 1 pediatric trauma center in the United States. PATIENTS: Children admitted for severe traumatic brain injury from 2006 to 2016 who received 23.4% hypertonic saline and whose intracranial pressures were measured within 5 hours of receiving 23.4% hypertonic saline. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Over the 10-year period, 1,587 children were admitted for traumatic brain injury, 155 of whom were deemed severe per this study's criteria. Forty of these children received at least one dose of hypertonic saline, but 14 were excluded for insufficient intracranial pressure data. Among the remaining 26 children, one hundred one 23.4% hypertonic saline boluses were used in the analysis. Use of 23.4% hypertonic saline was associated with a decrease in intracranial pressure of approximately 7 mm Hg at both within 1 hour after the bolus (p < 0.01) and 4 hours after the bolus (p < 0.01) when compared with the intracranial pressure measured within 1 hour before the hypertonic saline bolus. These effects remained significant after adjusting for Functional Status Scale score and CT Marshall scores. There was no statistically significant association between adjunctive therapies, such as antiepileptics and analgesics, and changes in intracranial pressure. There was no laboratory evidence of hyperkalemia or renal injury after use of 23.4% hypertonic saline. Across all hospitalizations, 65% of the study population demonstrated an abnormally elevated creatinine at least once, but only three episodes of acute kidney injury occurred in total, all before hypertonic saline administration. Eight of the 26 children in this analysis died during their hospitalization. The Functional Status Scale scores ranged from 6 to 26 with a mean of 12.2 and SD of 5.7. CONCLUSIONS: Use of 23.4% hypertonic saline with children admitted for severe traumatic brain injury is associated with a statistically significant decrease in intracranial pressure within 1 hour of use.

Accelerated Brain Atrophy on Serial Computed Tomography: Potential Marker of the Progression of Alzheimer Disease.

OBJECTIVE: The aim of this study was to validate computed tomography (CT)-based longitudinal markers of the progression of Alzheimer disease (AD). MATERIALS AND METHODS: We retrospectively studied 33 AD patients and 39 nondemented patients with other neurological illnesses (non-AD) having 4 to 12 CT examinations of the head, with over a mean (SD) of 3.9 (1.7) years. At each time point, we applied an automatic software to measure whole brain, cerebrospinal fluid, and intracranial space volumes. Longitudinal measures were then related to disease status and time since the first scan using hierarchical models. RESULTS: Absolute brain volume loss accelerated for non-AD patients by 0.86 mL/y (95% confidence interval [CI], 0.64-1.08 mL/y) and 1.5× faster, that is, 1.32 mL/y (95% CI, 1.09-1.56 mL/y) for AD patients (P = 0.006). In terms of brain volume normalized to intracranial space, the acceleration in atrophy rate for non-AD patients was 0.0578%/y (95% CI, 0.0389%/y to 0.0767%/y), again 1.5× faster, that is, 0.0919%/y (95% CI, 0.0716%/y to 0.1122%/y) for AD patients (P = 0.017). This translates to an increase in atrophy rate from 0.5% to 1.4% in AD versus to 1.1% in non-AD group after 10 years. CONCLUSIONS: Brain volumetry on CT reliably detected accelerated volume loss in AD and significantly lower acceleration factor in age-matched non-AD patients, leading to the possibility of its use to monitor the progression of cognitive decline and dementia.

A ventriculomegaly feature computational pipeline to improve the screening of normal pressure hydrocephalus on CT.

OBJECTIVE: The objective of this study was to develop a computational pipeline that extracts objective features of ventriculomegaly from non-contrast CT (NCCT) for the accurate classification of idiopathic normal pressure hydrocephalus (NPH) from headache controls (HCs), Alzheimer's dementia (AD), and posttraumatic encephalomalacia (PTE). METHODS: Patients with possible NPH (n = 79) and a subset with definite NPH (DefNPH; n = 29) were retrospectively identified in the Veterans Affairs Informatics and Computing Infrastructure system, along with the AD (n = 62), PTE (n = 53), and HC (n = 59) cohorts. Image-processing pipelines were developed to extract a novel feature capturing the maximum eccentricity of the lateral ventricles (MaxEccLV), a proxy splenial angle (p-SA), the Evans indices (EI-x, -y, and -z), callosal angle, normalized maximum third-ventricle width, and CSF to brain volume ratio from their NCCT scans. The authors used t-tests to examine group differences in the features and multivariate logistic regression models for classification. Additionally, the NPH versus HC classifier was validated on external data. RESULTS: When NPH and DefNPH were compared with HC, AD, and PTE, significant differences were found in all features except the p-SA, which only significantly differed between NPH and PTE. The test-set area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were 0.98, 100%, and 98.3% for NPH versus HC classification; 0.94, 87.3%, and 85.5% for NPH versus AD; 0.96, 92.4%, and 90.6% for NPH versus PTE; and 0.96, 94%, and 88% for NPH versus the other groups using logistic regression under five-fold cross-validation. Consistently high performance was noted for DefNPH. The NPH versus HC classifier provided an AUC of 0.84, sensitivity of 76.9%, and specificity of 90% when assessed on external data. CONCLUSIONS: Including the novel MaxEccLV, this framework computes useful features of ventriculomegaly, which had not previously been algorithmically assessed on NCCT. This framework successfully classified possible and definite NPH from HC, AD, and PTE. Following validation on larger representative cohorts, this objective and accessible tool may aid in screening for NPH and differentiating it from symptomatic mimics such as AD and PTE.

Structural neuroimaging markers of normal pressure hydrocephalus versus Alzheimer's dementia and Parkinson's disease, and hydrocephalus versus atrophy in chronic TBI-a narrative review.

Introduction: Normal Pressure Hydrocephalus (NPH) is a prominent type of reversible dementia that may be treated with shunt surgery, and it is crucial to differentiate it from irreversible degeneration caused by its symptomatic mimics like Alzheimer's Dementia (AD) and Parkinson's Disease (PD). Similarly, it is important to distinguish between (normal pressure) hydrocephalus and irreversible atrophy/degeneration which are among the chronic effects of Traumatic Brain Injury (cTBI), as the former may be reversed through shunt placement. The purpose of this review is to elucidate the structural imaging markers which may be foundational to the development of accurate, noninvasive, and accessible solutions to this problem. Methods: By searching the PubMed database for keywords related to NPH, AD, PD, and cTBI, we reviewed studies that examined the (1) distinct neuroanatomical markers of degeneration in NPH versus AD and PD, and atrophy versus hydrocephalus in cTBI and (2) computational methods for their (semi-) automatic assessment on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans. Results: Structural markers of NPH and those that can distinguish it from AD have been well studied, but only a few studies have explored its structural distinction between PD. The structural implications of cTBI over time have been studied. But neuroanatomical markers that can predict shunt response in patients with either symptomatic idiopathic NPH or post-traumatic hydrocephalus have not been reliably established. MRI-based markers dominate this field of investigation as compared to CT, which is also reflected in the disproportionate number of MRI-based computational methods for their automatic assessment. Conclusion: Along with an up-to-date literature review on the structural neurodegeneration due to NPH versus AD/PD, and hydrocephalus versus atrophy in cTBI, this article sheds light on the potential of structural imaging markers as (differential) diagnostic aids for the timely recognition of patients with reversible (normal pressure) hydrocephalus, and opportunities to develop computational tools for their objective assessment.

PaCO2 Association with Traumatic Brain Injury Patients Outcomes at High Altitude: A Prospective Single-Center Cohort Study.

Background: partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. Methods: This is a prospective single-center cohort of consecutive TBI patients admitted to a trauma center located at 2600 meter above sea level. An unfavorable outcome was defined as the Glasgow Outcome Scale-Extended (GOSE) < 4 at 6-month follow-up. Results: 81 patients with complete data, 80% (65/81) were men, and median (IQR) age was 36 (25-50) years). Median Glasgow Coma Scale (GCS) on admission was 9 (6-14), 49% (40/81) were severe (GCS: 3-8), 32% (26/81) moderate (GCS 12 - 9), and 18% (15/81) mild (GCS 13-15) TBI. The median (IQR) Abbreviated Injury Score of the Head (AISh) was 3 (2-4). Frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), median GOSE was 4 (2-5), and 6-month mortality was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, median [49 (30-72) vs. 29 (22-41), P < 0.01], had lower admission GCS [6 (4-8) vs. 13 (8-15), P < 0.01], higher AIS head [4 (4-4) vs. 3(2-4), p < 0.01], higher APACHE II score [17(15-23) vs 10 (6-14), < 0.01), higher Charlson score [0(0-2) vs. 0 (0-0), P < 0.01] and higher PaCO2 (mmHg), mean ± SD, 39 ± 9 vs. 32 ± 6, P < 0.01. In a multivariate analysis, age (OR 1.14 95% CI 1.1-1.30, P < 0.01), AISh (OR 4.7 95% CI 1.55-21.0, P < 0.05), and PaCO2 (OR 1.23 95% CI: 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4 95% CI: 1.61-28.5, P = 0.017) and PaCO2 (OR 1.36 95% CI: 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. Conclusion: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated TBI patients. These results underscore the importance of PaCO2 level in TBI patients and whether it should be adjusted for populations living at higher altitudes.

An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

Recovery of volitional movement with epidural stimulation after "complete" spinal cord injury due to gunshot: A case report and literature review.

Background: Epidural spinal cord stimulation (eSCS) restores volitional movement and improves autonomic function after nonpenetrating and traumatic spinal cord injury (SCI). There is limited evidence of its utility for penetrating SCI (pSCI). Case Description: A 25-year-old male sustained a gunshot wound (GSW) resulting in T6 motor/sensory paraplegia and complete loss of bowel and bladder function. Following eSCS placement, he regained partial volitional movement and has independent bowel movements 40% of the time. Conclusion: A 25-year-old pSCI patient who, following a GSW resulting in T6-level paraplegia, sustained marked recovery of volitional movement and autonomic function following eSCS placement.

Neuromodulation Through Spinal Cord Stimulation Restores Ability to Voluntarily Cycle After Motor Complete Paraplegia.

Abstract Epidural spinal cord stimulation (eSCS) of the lower thoracic spinal cord has been shown to partially restore volitional movement in patients with complete chronic spinal cord injury (cSCI). Combining eSCS with intensive locomotor training improves motor function, including standing and stepping, but many patients with cSCI suffer from long-standing muscle atrophy and loss of bone mineral density, which may prohibit safe implementation. Safe, accessible, and effective avenues for pairing neuromodulation with activity-based therapy remain unexplored. Cycling is one such option that can be utilized as an eSCS therapy given its low-risk and low-weight-bearing requirement. We investigated the feasibility and kinematics of motor-assisted and passive cycle-based therapy for cSCI patients with epidural spinal cord stimulation. Seven participants who underwent spinal cord stimulation surgery in the Epidural Stimulation After Neurologic Damage (E-STAND) trial (NCT03026816) participated in a cycling task using the motor assist MOTOmed Muvi 300. A factorial design was used such that participants were asked to cycle with and without conscious effort with and without stimulation. We used mixed effects models assessing maximum power output and time pedaling unassisted to evaluate the interaction between stimulation and conscious effort. Cycling was well-tolerated and we observed no adverse events, including in participants up to 17 years post-initial injury and up to 58 years old. All participants were found to be able to pedal without motor assist, which primarily occurred when stimulation and effort were applied together (p = 0.001). Additionally, the combination of stimulation and intention was significantly associated with higher maximum power production (p < 0.0001) and distance pedaled (p = 0.0001). No association was found between volitional movement and participant factors: age, time since injury, and spinal cord atrophy. With stimulation and conscious effort, all participants were able to achieve active cycling without motor assistance. Thus, our stationary cycling factorial study design demonstrated volitional movement restoration with eSCS in a diverse study population of cSCI participants. Further, motor-assist cycling was well-tolerated without any adverse events. Cycling has the potential to be a safe research assessment and physical therapy modality for cSCI patients utilizing eSCS who have a high risk of injury with weight bearing exercise. The cycling modality in this study was demonstrated to be a straightforward assessment of motor function and safe for all participants regardless of age or time since initial injury.

Effect of epidural spinal cord stimulation on female sexual function after spinal cord injury.

Sexual dysfunction is a common consequence for women with spinal cord injury (SCI); however, current treatments are ineffective, especially in the under-prioritized population of women with SCI. This case-series, a secondary analysis of the Epidural Stimulation After Neurologic Damage (E-STAND) clinical trial aimed to investigate the effect of epidural spinal cord stimulation (ESCS) on sexual function and distress in women with SCI. Three females, with chronic, thoracic, sensorimotor complete SCI received daily (24 h/day) tonic ESCS for 13 months. Questionnaires, including the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) were collected monthly. There was a 3.2-point (13.2%) mean increase in total FSFI from baseline (24.5 ± 4.1) to post-intervention (27.8 ± 6.6), with a 4.8-50% improvement in the sub-domains of desire, arousal, orgasm and satisfaction. Sexual distress was reduced by 55%, with a mean decrease of 12 points (55.4%) from baseline (21.7 ± 17.2) to post-intervention (9.7 ± 10.8). There was a clinically meaningful change of 14 points in the International Standards for Neurological Classification of Spinal Cord Injury total sensory score from baseline (102 ± 10.5) to post-intervention (116 ± 17.4), without aggravating dyspareunia. ESCS is a promising treatment for sexual dysfunction and distress in women with severe SCI. Developing therapeutic interventions for sexual function is one of the most meaningful recovery targets for people with SCI. Additional large-scale investigations are needed to understand the long-term safety and feasibility of ESCS as a viable therapy for sexual dysfunction. Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03026816, NCT03026816.

Cerebral atrophy is associated with development of chronic subdural haematoma.

OBJECTIVE: To test that cerebral atrophy is associated with increased risk for development of chronic subdural haematoma (cSDH), this study performed volumetric analysis of computed tomography (CT) brain scans from patients who were diagnosed with cSDH on subsequent CT scans and their age-matched controls. METHODS: Volumetric analysis was performed on CT scans acquired a mean of 209 days prior to cSDH diagnosis in 19 patients. Cerebral atrophy present on these scans was then compared to 76 age-matched control patients randomly selected from cSDH-free subjects. RESULTS: There was a higher degree of atrophy in cSDH patients (n = 19, 14.3% ± 5.4%) than in age-matched control patients (n = 76, 11.9% ± 5.5%; p = 0.044). Logistical regression demonstrated that atrophy was found to be a significant predictor of cSDH at all ages (OR = 1.11, 95% CI = [1.01, 1.23], p = 0.05). For younger subjects ≤65 years of age (n = 50), atrophy was an even stronger predictor of cSDH (OR = 1.17, 95% CI = [1.02, 1.34], p = 0.026). CONCLUSIONS: Cerebral atrophy is associated with the development of cSDH and this association is greater in patients ≤65 years of age.

Resection of disseminated recurrent myxopapillary ependymoma with more than 4-year follow-up: operative nuance for prolonged prone position. Illustrative case.

BACKGROUND: Symptomatic disseminated myxopapillary ependymoma (MPE) in a young person presents a daunting challenge because the risks of prolonged prone positioning and spinal cord injury may outweigh the likelihood of attaining the benefit of gross total resection. OBSERVATIONS: The authors reported the case of a 15-year-old girl with five discrete recurrent spinal cord ependymomas. The patient received a 25-hour surgical procedure for gross total resection of the tumors and fusion over an approximately 33-hour period. She experienced complete resolution of all preoperative neurological symptoms and subsequently received adjuvant radiation therapy. At 52 months after surgery, she was still experiencing neurologically intact, progression-free survival. This case illustrated one of the most extensive recurrent tumor resections for MPE with prolonged disease-free survival reported to date. It may also represent the longest prone position spinal case reported and was notable for a lack of any of the complications commonly associated with the prolonged prone position. LESSONS: The authors discussed the complexity of surgical decision-making in a symptomatic patient with multiple disseminated metastases, technical considerations for resection of intradural and intramedullary spinal cord tumors, and considerations for avoiding complications during prolonged positioning necessary for spinal surgery.

Eye tracking for classification of concussion in adults and pediatrics.

Introduction: In order to obtain FDA Marketing Authorization for aid in the diagnosis of concussion, an eye tracking study in an intended use population was conducted. Methods: Potentially concussed subjects recruited in emergency department and concussion clinic settings prospectively underwent eye tracking and a subset of the Sport Concussion Assessment Tool 3 at 6 sites. The results of an eye tracking-based classifier model were then validated against a pre-specified algorithm with a cutoff for concussed vs. non-concussed. The sensitivity and specificity of eye tracking were calculated after plotting of the receiver operating characteristic curve and calculation of the AUC (area under curve). Results: When concussion is defined by SCAT3 subsets, the sensitivity and specificity of an eye tracking algorithm was 80.4 and 66.1%, The AUC was 0.718. The misclassification rate (n = 282) was 31.6%. Conclusion: A pre-specified algorithm and cutoff for diagnosis of concussion vs. non-concussion has a sensitivity and specificity that is useful as a baseline-free aid in diagnosis of concussion. Eye tracking has potential to serve as an objective "gold-standard" for detection of neurophysiologic disruption due to brain injury.